What makes us drink?: Alcohol consumption in the rat in connection with reward and cognition

Abstract

Alcohol use disorder (AUD; often referred to as alcohol addiction or alcoholism) is a chronic relapsing brain disorder characterized by loss of control over alcohol intake. Alcohol is among the most widely used substances in the world, and even though only a minority of the people who regularly consume alcohol develop AUD, this still amounts to approximately 76 million people worldwide. Importantly, it is still unclear why some individuals are more at risk for AUD than others. The development of AUD is thought to involve a complex interaction between personality characteristics, the environment of an individual and long-lasting alcohol-induced changes in brain function. The overarching aim of this thesis was to determine which factors contribute to the individual vulnerability for AUD, using studies in rats. One of the main findings is that in populations of rats, we could identify animals that voluntarily drink low or high quantities of alcohol. We observed that a high voluntary alcohol consumption was related to a higher motivation to obtain alcohol and a loss of control over alcohol seeking, a key characteristic of AUD. Moreover, cognitive assessments showed that high alcohol consumption was related to reward-directed behaviour in decision making tasks and an enhanced focus on reward cues. In addition, we observed that a disrupted social development increases alcohol consumption during adulthood. With regard to the brain mechanisms involved, we investigated the role of the mesolimbic dopamine system, which is thought to play an important role in addictive behaviour. We found that functional activity of the mesolimbic dopamine system is of great importance for the motivation to obtain alcohol, but not for the individual level of alcohol consumption. Interestingly, the mesolimbic dopamine system was more sensitive to rewards and reward cues in rats that have been exposed to alcohol during adolescence. In conclusion, the results in this thesis contribute to the understanding of the behavioural, cognitive, social and brain mechanisms that underlie the risk for AUD. Therefore, these studies may help the development of improved treatment strategies to restore control over alcohol use.